Previous studies in our laboratory have shown that human intestinal mucosal T cells have little expression of the Leu-8 antigen which is normally found on the majority of peripheral blood T cells. In addition, CD4+, Leu-8+ T cells were shown to directly suppress immunoglobulin (Ig) synthesis, whereas CD4+, Leu-8 negative T cells provide help for immunoglobulin synthesis. It was also shown that modulation of the Leu-8 antigen with monoclonal anti-Leu-8 antibody enhances the suppressor function of CD4 T cells. To further examine the functional significance of decreased expression of the Leu-8 antigen on intestinal mucosal T cells, in the present study we compared the helper and suppressor function of lamina propria lymphocytes. At high T/B cell ratios, it was found that intestinal T cells provided more help for Ig synthesis than peripheral T cells. Whereas pretreatment of peripheral blood cells with anti-Leu-8 under crosslinking conditions significantly inhibited Ig synthesis, pretreatment of intestinal lymphocytes did not. In further studies of the mechanism of this phenomenon, CD4 T cells were isolated and tested for suppressor function following treatment with anti-Leu- 8; it was found that peripheral blood, but not lamina propria CD4 T cells suppressed Ig synthesis. When highly purified populations of CD4+, Leu-8 negative and CD4+, Leu-8+ T cells were prepared from peripheral blood and intestinal lamina propria, it was found that the peripheral blood and intestinal T cell subpopulations had similar helper and suppressor function, respectively. Thus, the diminished suppressor function of intestinal CD4 T cells is due to the diminished number of CD4, Leu-8+ T cells in the lamina propria rather than any intrinsic difference in their function. This difference in T cell function in the intestine may be important for immunoglobulin production in the mucosa and in the understanding of intestinal inflammation in IBD.